So-called “good fatty acids” are essential for human health and are highly sought after by those who try to eat healthily. Among omega-3 fatty acids, DHA or docosahexaenoic acid is crucial for brain function, vision and the regulation of inflammatory phenomena.
In addition to these virtues, DHA has been linked to reducing the incidence of cancer. The way it works is the subject of a major discovery by a multidisciplinary team of researchers from the University of Louvain (UCLouvain) who have just elucidated the biochemical mechanism that allows DHA and other related fatty acids to slow the growth of tumors. This is a major advance that was recently published in a prestigious magazine Cellular metabolism.
Key to discovery: interdisciplinarity
In 2016, Olivier Feron’s team at UCLouvain, which specializes in oncology, discovered that cells in an acidic microenvironment (acidosis) in tumors replace glucose with lipids as an energy source to multiply. In collaboration with Cyril Corbett of UCLouvain, Prof. Ferron demonstrated in 2020 that these same cells are the most aggressive and acquire the ability to leave the original tumor to generate metastases. Meanwhile, Yvan Larondelle, a professor at the Faculty of Bioengineering at UCLouvain, whose team develops advanced nutritional sources of lipids, suggested that Prof. Feron combine their skills in a research project led by PhD candidate Emeline Dierge to assess tumor cell behavior. of various fatty acids.
3D tumors that disintegrate within a few days thanks to the action of the well-known Omega-3 (DHA, found mainly in fish) – this is the exclusive discovery of the University of Louvain. Hungry for fatty acids, tumor cells in acidosis appear on DHA, but are unable to store it properly and are literally poisoned. The result? They are dying. Credit: UCLouvain Copyright
Thanks to the support of the Leuven Foundation, the Belgian Cancer Foundation and the Télévie telephone, the team quickly found that these acidotic tumor cells reacted in diametrically opposite ways depending on the fatty acid they absorbed. Within a few weeks, the results were both impressive and surprising. “We recently found that some fatty acids stimulate tumor cells, while others kill them,” the researchers explained. DHA literally poisons them.
The poison acts on tumor cells through a phenomenon called ferroptosis, a type of cell death associated with the peroxidation of certain fatty acids. The greater the amount of unsaturated fatty acids in the cell, the greater the risk of their oxidation. Usually in the acid compartment in tumors, cells store these fatty acids in lipid droplets, a type of bundle in which fatty acids are protected from oxidation. But in the presence of large amounts of DHA, the tumor cell is overloaded and cannot store DHA, which oxidizes and leads to cell death. Using an inhibitor of lipid metabolism, which prevents the formation of lipid droplets, the researchers were able to notice that this phenomenon is further enhanced, which confirms the established mechanism and opens the door to the possibility of combined treatment.
For their study, UCLouvain researchers used a 3D system for culturing tumor cells called spheroids. In the presence of DHA, spheroids first grow and then implode. The team also administered a DHA-enriched diet to tumor mice. The result: tumor development was significantly delayed compared to mice on a conventional diet.
This study by UCLouvain shows the value of DHA in the fight against cancer. “For an adult,” said UCLouvain researchers, “it is recommended that you consume at least 250 mg of DHA per day.” But studies show that our diet provides an average of only 50 to 100 mg per day. This is well below the minimum recommended intake. “
Reference: June 11, 2021, Cellular metabolism.
DOI: 10.1016 / j.cmet.2021.05.016